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Schroder FH, Hugosson J, Roobol MJ, et al, for the ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; published online Aug 7. http://dx.doi.org/10.1016/ S0140-6736(14)60525-0. Powell IJ, Bock CH, Ruterbusch JJ, Sakr W. Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. J Urol 2010; 183: 1792–97. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4·0 ng per milliliter. N Engl J Med 2004; 350: 2239–46. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate cancer survivors. N Engl J Med 2008; 358: 1250–61. Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28: 126–31.
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Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006; 296: 2329–35. Roach M 3rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 2008; 26: 585–91. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008; 299: 289–95. Wilt TJ, Brawer MK, Jones KM, et al, for the Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203–13. Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst 2006; 98: 529–34.
Dr P Marazzi/Science Photo Library
Ponesimod—a future oral therapy for psoriasis?
Psoriasis Published Online August 11, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)61039-4 See Articles page 2036
2006
Increased understanding of the role of sphingosine1-phosphate (S1P) in modulating the circulation of T lymphocytes has led to development of a new class of targeted therapies for psoriasis.1 In The Lancet, Andrea Vaclavkova and colleagues2 report on a phase 2 study of ponesimod, the first oral selective modulator of the S1P receptor 1 (S1PR1), for the treatment of chronic plaque psoriasis. S1P is a lysophospholipid whose activity is mediated through five G-protein-coupled S1P receptors, and ponesimod is a selective S1PR1 antagonist that depletes surface S1PR1 and prevents T-lymphocyte egress from secondary lymphoid tissues into the circulation. Ponesimod and fingolimod, another antagonist of S1PR1, have successfully been used to treat multiple sclerosis, which is a T-helper-17-mediated inflammatory disease, like psoriasis.3,4 Vaclavkova and colleagues included 326 patients in a randomised, double-blind, placebo-controlled trial. The primary endpoint of a 75% reduction in psoriasis area and severity index score from baseline (PASI75) was achieved after 16 weeks in 58 (46·0%) of 126 patients treated with 20 mg ponesimod daily and in 64 (48·1%) of 133 patients treated with 40 mg ponesimod daily, compared with nine (13·4%) of 67 patients who received placebo (both differences p
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Schroder FH, Hugosson J, Roobol MJ, et al, for the ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; published online Aug 7. http://dx.doi.org/10.1016/ S0140-6736(14)60525-0. Powell IJ, Bock CH, Ruterbusch JJ, Sakr W. Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. J Urol 2010; 183: 1792–97. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4·0 ng per milliliter. N Engl J Med 2004; 350: 2239–46. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate cancer survivors. N Engl J Med 2008; 358: 1250–61. Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28: 126–31.
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Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006; 296: 2329–35. Roach M 3rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 2008; 26: 585–91. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008; 299: 289–95. Wilt TJ, Brawer MK, Jones KM, et al, for the Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203–13. Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst 2006; 98: 529–34.
Dr P Marazzi/Science Photo Library
Ponesimod—a future oral therapy for psoriasis?
Psoriasis Published Online August 11, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)61039-4 See Articles page 2036
2006
Increased understanding of the role of sphingosine1-phosphate (S1P) in modulating the circulation of T lymphocytes has led to development of a new class of targeted therapies for psoriasis.1 In The Lancet, Andrea Vaclavkova and colleagues2 report on a phase 2 study of ponesimod, the first oral selective modulator of the S1P receptor 1 (S1PR1), for the treatment of chronic plaque psoriasis. S1P is a lysophospholipid whose activity is mediated through five G-protein-coupled S1P receptors, and ponesimod is a selective S1PR1 antagonist that depletes surface S1PR1 and prevents T-lymphocyte egress from secondary lymphoid tissues into the circulation. Ponesimod and fingolimod, another antagonist of S1PR1, have successfully been used to treat multiple sclerosis, which is a T-helper-17-mediated inflammatory disease, like psoriasis.3,4 Vaclavkova and colleagues included 326 patients in a randomised, double-blind, placebo-controlled trial. The primary endpoint of a 75% reduction in psoriasis area and severity index score from baseline (PASI75) was achieved after 16 weeks in 58 (46·0%) of 126 patients treated with 20 mg ponesimod daily and in 64 (48·1%) of 133 patients treated with 40 mg ponesimod daily, compared with nine (13·4%) of 67 patients who received placebo (both differences p
